Background: The 2026 American Heart Association/American College of Cardiology (AHA/ACC) Pulmonary Embolism Guideline (Creager et al., Circulation 2026) introduced a novel five-category (A-E) clinical classification system with subcategories and an R modifier, replacing prior risk stratification frameworks. Prospective validation of this classification system using composite clinical outcomes is lacking. Objective: To evaluate the prognostic value of the 2026 AHA/ACC clinical categorization (Categories A-E plus R modifier) for predicting 30-day Major Adverse Pulmonary Embolism Events (MAPEE) in emergency department (ED) patients with acute pulmonary embolism (PE). Methods: Prospective observational cohort study conducted at Marmara University Faculty of Medicine Emergency Department, enrolling 600 consecutive adult patients with confirmed acute PE by computed tomography (CT) pulmonary angiography between April 2026 and January 2027. Primary outcome: MAPEE composite (all-cause mortality OR hemodynamic deterioration OR treatment escalation OR cardiopulmonary resuscitation) within 30 days. Secondary outcomes include area under the receiver operating characteristic curve (AUC) comparison with the European Society of Cardiology (ESC) 2019 risk stratification (exploratory), negative predictive value (NPV) of low-risk categories (A+B) for safe discharge, MAPEE trend across C1/C2/C3, and R modifier odds ratio. Statistical analysis: Jamovi v2.x. Reporting follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 2007 checklist.
Age >=18 years
Confirmed acute PE on CT pulmonary angiography (CTPA) within 24 hours of ED presentation
Informed consent obtained
Ability to complete 30-day follow-up
Chronic thromboembolic pulmonary hypertension (CTEPH)
Age <18 years
Pregnancy
Incomplete CTPA or non-diagnostic imaging
Adult patients (\>=18 years) presenting to Marmara University Pendik Training and Research Hospital Emergency Department with confirmed acute pulmonary embolism on CTPA between April 2026 and January 2027.
Cohort
Prospective
2026 AHA/ACC Clinical Risk Categorization
Other interventionNot a therapeutic intervention. Refers to the 2026 AHA/ACC clinical categorization framework (Categories A-E plus R modifier for right ventricular strain) applied at presentation to prognostically classify patients with confirmed acute pulmonary embolism. All patients are managed per standard institutional practice; no protocol-driven treatment or diagnostic assignment is made based on this categorization.
Major Adverse Pulmonary Embolism Event (MAPEE) - 30-day composite
Composite of: (1) all-cause mortality, OR (2) hemodynamic deterioration (SBP \<90 mmHg for \>=15 minutes or vasopressor requirement), OR (3) treatment escalation (systemic thrombolysis, catheter-directed therapy, surgical embolectomy, or ECMO), OR (4) cardiopulmonary resuscitation - within 30 days of ED presentation.
S1: AHA/ACC vs ESC 2019 ROC-AUC comparison (exploratory)
Comparison of ROC-AUC: 2026 AHA/ACC A-E system vs ESC 2019 risk stratification for MAPEE prediction (DeLong test - EXPLORATORY/hypothesis-generating; n=600 enrollment marginally below the 621 required for 80% power at H1=0.80; no superiority claim will be made).
S2: NPV of AHA/ACC Category A+B for MAPEE
Negative Predictive Value (NPV) of AHA/ACC Category A+B for MAPEE, evaluating potential for safe emergency department discharge without hospital admission.
S3: MAPEE trend across AHA/ACC subcategories C1, C2, C3
Linear MAPEE event rate trend across AHA/ACC subcategories C1, C2, and C3, assessed via Cochran-Armitage trend test.
S4: Odds ratio for MAPEE by R modifier status
Odds ratio (OR) and likelihood ratio (LR+/LR-) for MAPEE in patients with vs without the R modifier (right ventricular strain) at presentation.
Click on the lead sponsor to view all of their trials.
